Skip to main content
SpringerLink
Log in

Biodegradable PEGylated microspheres and nanospheres

  • Healthcare Technology Review
  • Published:
American Journal of Drug Delivery

Abstract

The area of drug delivery through biodegradable microspheres and nanospheres has grown immensely in the past few years. The inherent limitation of these delivery systems in prolonging the release of the encapsulated drug is their uptake by the macrophages (located in the mononuclear phagocyte system) mainly in the liver and spleen. This factor limits their circulation time and hence the clinical effectiveness of the encapsulated drug. Therefore an agent is needed that can provide a chemical camouflage to these microspheres and nanospheres in order to make them long-circulating carriers.

Polyethylene glycol (PEG), a hydrophilic, US FDA-approved polymer, provides the solution to this difficult problem. Biodegradable microspheres and nanospheres possessing a hydrophilic, dysopsonic, PEG-based coating are suitable candidates for the fabrication of long-circulating carriers and have modified pharmacokinetic and pharmacodynamic properties that lead to an increase in the clinical effectiveness of the encapsulated drug. This review discusses the rationale behind the development of PEGylated microspheres and nanospheres and provides an insight into their preparation, characterization, and various drugs/proteins encapsulated in such systems. The PEGylated preparations currently available on the market and those that are about to enter the market are also discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Table II
Fig. 1

Similar content being viewed by others

Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

References

  1. Diepold R, Kreuter J, Guggenbuhl P, et al. Distribution or poly-hexyl-2-cyano-[3-14C] acrylate nanoparticles in healthy and chronically inflamed rabbit eyes. Int J Pharm 1989; 54: 149–53

    Article  CAS  Google Scholar 

  2. Illum L, Wright J, Davis SS. Targeting of microspheres to sites of inflammation. Int J Pharm 1989; 52: 221–4

    Article  CAS  Google Scholar 

  3. Alpar HO, Field WN, Hyde R, et al. The transport of microspheres from the gastrointestinal tract to inflammatory air pouches in the rat. J Pharm Pharmacol 1989; 41: 194–6

    Article  PubMed  CAS  Google Scholar 

  4. Gref R, Minamitake Y, Peracchia M, et al. Biodegradable long-circulating nanospheres. Science 1994; 263: 1600–3

    Article  PubMed  CAS  Google Scholar 

  5. Couvreur P, Kante B, Grislain L, et al. Toxicity of polyalkylcyanoacrylate nanoparticles: II. Doxorubicin loaded nanoparticles. J Pharm Sci 1982; 71: 790–2

    Article  PubMed  CAS  Google Scholar 

  6. Akerman ME, Chan WCW, Laakkonen P, et al. Nanocrystal targeting in vivo. Proc Natl Acad Sci U S A 2002; 99: 12617–21

    Article  PubMed  CAS  Google Scholar 

  7. Gref R, Minamitake Y, Peracchia MT, et al. Poly(ethylene glycol)-coated biodegradable nanospheres for intravenous drug administration. In: Cohen S, Bernstein H, editors. Microparticulate systems for delivery of proteins and vaccines. New York: Marcel Dekker Inc., 1996: 279–306

    Google Scholar 

  8. Malmstein M. Protein adsorption at phospholipid surfaces. J Colloid Interface Sci 1995; 172: 106–15

    Article  Google Scholar 

  9. Illum L, Davis S, Muller R, et al. The organ distribution and circulation time of intravenously injected colloidal carriers sterically stabilized with a block co-polymer-poloxamine 908. Life Sci 1987; 40: 367–74

    Article  PubMed  CAS  Google Scholar 

  10. Bazile D, Ropert C, Huve P, et al. Body distribution of fully biodegradable 14C-poly(lactic acid) nanoparticles coated with albumin after parenteral administration to rats. Biomaterials 1992; 13: 1093–102

    Article  PubMed  CAS  Google Scholar 

  11. Kreuter J, Tauber U, Illi V. Distribution and elimination of poly(methyl-2-14C-methacrylate) nanoparticles radioactivity after injection in rats and mice. J Pharm Sci 1979; 68: 1443–7

    Article  PubMed  CAS  Google Scholar 

  12. Munthe-Kaas AC, Kaplan G. Endocytosis by macrophages. In: Friedman H, Escoban M, Reichard SM, editors. The reticuloendothelial system, a comprehensive treatise. New York: Plenum Press, 1980: 19–55

    Google Scholar 

  13. Artursson P, Sjoholm I. Effect of opsonins on the macrophage uptake of polyacryl-starch microparticles. Int J Pharm 1986; 32: 165–70

    Article  CAS  Google Scholar 

  14. Leroux JC, DeJaeghere F, Anner B, et al. An investigation of the role of plasma and serum opsonins on the internalization of biodegradable poly (D,L-lactic acid) nanoparticles by human monocytes. Life Sci 1995; 57: 695–703

    Article  PubMed  CAS  Google Scholar 

  15. Kreuter J. Evaluation of nanoparticles as drug-delivery systems: III. Materials, stability, toxicity, possibilities of targeting and use. Pharm Acta Helv 1983; 58: 242–50

    PubMed  CAS  Google Scholar 

  16. Illum L, Davis S. Effect of the nonionic surfactant poloxamer 338 on the fate and deposition of polystyrene microspheres following intravenous administration. J Pharm Sci 1983; 72: 1086–9

    Article  PubMed  CAS  Google Scholar 

  17. Wilkins D, Myers P. Studies on the relationship between the electrophoretic properties of colloids and their blood clearance and organ distribution in the rat. Br J Exp Pathol 1966; 47: 568–76

    PubMed  CAS  Google Scholar 

  18. Leu D, Manthey B, Kreuter J, et al. Distribution and elimination of coated polymethyl (2-14C) methacrylate nanoparticles after intravenous administration in rats. J Pharm Sci 1984; 73: 1433–7

    Article  PubMed  CAS  Google Scholar 

  19. Dunn S, Brindley A, Davis S, et al. Polystyrene-poly(ethylene glycol)(PSPEG2000) particles as model systems for site specific drug delivery: 2. The effect of PEG surface density on the in vitro cell interaction and in vivo biodistribution. Pharm Res 1994; 11: 1016–22

    Article  PubMed  CAS  Google Scholar 

  20. Allen T, Hansen C, Rutledge J. Liposomes with prolonged circulation times: factors affecting uptake by reticuloendothelial and other tissues. Biochim Biophys Acta 1989; 981: 27–35

    Article  PubMed  CAS  Google Scholar 

  21. Klibanov A, Maruyama K, Torchilin V, et al. Amphiphatic polyethylene glycols effectively prolong the circulation time of liposomes. FEBS Lett 1990; 268: 235–7

    Article  PubMed  CAS  Google Scholar 

  22. Allen T, Hansen C, Martin F, et al. Liposomes containing synthetic lipid derivatives of poly(ethylene glycol) show prolonged circulation half lives in vivo. Biochim Biophys Acta 1991; 1066: 29–36

    Article  PubMed  CAS  Google Scholar 

  23. Prime K, Whitesides G. Adsorption of proteins onto surfaces containing end-attached oligo (ethylene oxide): a model system using self assembled monolayers. J Am Chem Soc 1993; 115: 10714–21

    Article  CAS  Google Scholar 

  24. Llanos G, Sefton M. Immobilization of poly(ethylene glycol) onto poly-(vinylalcohol) hydrogel: 2. Evaluation of thrombogenicity. J Biomed Mater Res 1993; 27: 1383–91

    Article  PubMed  CAS  Google Scholar 

  25. Harris J. Laboratory synthesis of polyethylene glycol derivatives. Rev Macromol Chem Phys 1985; C25: 325–73

    Article  CAS  Google Scholar 

  26. Molineux G. PEGylation: engineering improved pharmaceuticals for enhanced therapy. Cancer Treat Rev 2002; 28: 13–6

    Article  PubMed  CAS  Google Scholar 

  27. Harris JM, Chess RB. Effect of PEGylation on pharmaceuticals. Nat Rev Drug Discov 2003; 2: 214–21

    Article  PubMed  CAS  Google Scholar 

  28. Gref R, Minamitake Y, Peracchia MT,et al. Poly(ethylene glycol)-coated nanospheres: potential carriers for intravenous drug administration. In: Sanders LM, Hendren RW, editors. Protein delivery: physical systems. New York: Plenum Press, 1997: 167–98

    Google Scholar 

  29. Burnham NL. Polymers for delivering peptides and proteins. Am J Hosp Pharm 1994; 51: 210–8

    PubMed  CAS  Google Scholar 

  30. Harris JM, Martin NE, Modi M. PEGylation: a novel process for modifying pharmacokinetics. Clin Pharmacokinet 2001; 40: 539–51

    Article  PubMed  CAS  Google Scholar 

  31. Schellekens H. Immunogenicity of therapeutic proteins: clinical implications and future prospects. Clin Ther 2002; 24: 1720–40

    Article  PubMed  CAS  Google Scholar 

  32. Abuchowski A, Van ET, Palczuk N, et al. Alteration of immunological properties of bovine serum albumin by covalent attachment of polyethylene glycol. J Biol Chem 1977; 252: 3578–81

    PubMed  CAS  Google Scholar 

  33. Han D, Jeong S, Ahn K, et al. Preparation and surface properties of POE-sulfonate grafted polyurethanes for enhanced blood compatibility. J Biomater Sci Polym Ed 1993; 4: 579–89

    PubMed  CAS  Google Scholar 

  34. Sawhney A, Pathak C, Hubbell J. Interfacial photopolymerization of poly (ethylene glycol)-based hydrogels upon alginate poly (L-lysine) microcapsules for enhanced biocompatibility. Biomaterials 1993; 14: 1008–16

    Article  PubMed  CAS  Google Scholar 

  35. Quellec P, Gref R, Dellacherie E. Protein encapsulation within poly(ethylene glycol)-coated nanospheres: II. Controlled release properties. J Biomed Mater Res 1999; 47: 388–95

    Article  PubMed  CAS  Google Scholar 

  36. Diwan M, Park TG. PEGylation enhances protein stability during encapsulation in PLGA microspheres. J Control Release 2001; 73: 233–44

    Article  PubMed  CAS  Google Scholar 

  37. Jeon SI, Lee JH, Andrade JD, et al. Protein-surface interactions in the presence of polyethylene oxide: I. Simplified theory. J Colloid Interface Sci 1991; 142: 149–58

    Article  CAS  Google Scholar 

  38. Souhami RL, Patel HM, Ryman BE. The effect of reticuloendothelial blockade on the blood clearance and tissue distribution of liposomes. Biochim Biophys Acta 1981; 674: 354–71

    Article  PubMed  CAS  Google Scholar 

  39. Poste G. Liposome targeting in vivo: problems and opportunities. Biol Cell 1983; 47: 19–37

    CAS  Google Scholar 

  40. Kanke M, Simmons GH, Weiss DL, et al. Clearance of 141Ce labelled microspheres from blood and distribution in specific organs following intravenous and intra-arterial administration in beagle dogs. J Pharm Sci 1980; 69: 755–62

    Article  PubMed  CAS  Google Scholar 

  41. Davis SS. Colloids as drug delivery systems. J Pharm Technol 1981; 5: 71–88

    CAS  Google Scholar 

  42. Gregoriadis G, Neerunjun DE, Hunt R. Fate of liposome-associated agent injected into normal and tumour-bearing rodents: attempts to improve localization in tumour tissues. Life Sci 1977; 21: 357–70

    Article  PubMed  CAS  Google Scholar 

  43. Sato Y, Kiwada H, Kato Y. Effects of dose and vehicle size on the pharmacokinetics of liposomes. Chem Pharm Bull 1986; 34: 4244–52

    Article  PubMed  CAS  Google Scholar 

  44. Takino T, Konishi K, Takakura Y, et al. Long circulating emulsion carrier systems for highly lipophilic drugs. Biol Pharm Bull 1994; 17: 121–5

    Article  PubMed  CAS  Google Scholar 

  45. Tabata Y, Ikada Y. Macrophage phagocytosis of biodegradable microspheres composed of L-lactic acid/glycolic acid homo- and copolymers. J Biomed Mater Res 1988; 22: 837–58

    Article  PubMed  CAS  Google Scholar 

  46. Davis SS, Hansrani P. The influence of emulsifying agents on the phagocytosis of lipid emulsions by macrophages. Int J Pharm 1985; 23: 69–77

    Article  CAS  Google Scholar 

  47. Tabata Y, Ikada Y. Macrophage phagocytosis of biodegradable microspheres composed of L-lactic acid/glycolic acid homo- and copolymers. Biomaterials 1988; 9: 356

    Article  PubMed  CAS  Google Scholar 

  48. Bhadra D, Bhadra S, Jain P, et al. Pegnology: a review of PEG-ylated systems. Pharmazie 2002; 57: 5–29

    PubMed  CAS  Google Scholar 

  49. Blume G, Cevc G. Liposomes for the sustained drug release in vivo. Biochim Biophys Acta 1990; 1066: 91–7

    Google Scholar 

  50. Allen T. The use of glycolipids and hydrophilic polymers in avoiding rapid uptake of liposomes by the mononuclear phagocyte system. Adv Drug Deliv Rev 1994; 13: 285–309

    Article  CAS  Google Scholar 

  51. Maruyama K, Yuda T, Okamoto A, et al. Effect of molecular weight in amphiphatic polyethylene glycol on prolonging the circulation time of large unilamellar liposomes. Chem Pharm Bull 1991; 39: 1620–2

    Article  PubMed  CAS  Google Scholar 

  52. Woodle MC, Newman MS, Martin FJ. Liposome leakage and blood circulation: comparison of adsorbed block copolymers with covalent attachment of PEG. Int J Pharm 1992; 88: 327–34

    Article  CAS  Google Scholar 

  53. Massenburg D, Lentz B. Poly(ethylene glycol)-induced fusion and rupture of dipalmitoylphosphatidylcholine large unilamellar extruded vesicles. Biochemistry 1994; 32: 9172–80

    Article  Google Scholar 

  54. Gabizon A, Martin F. Polyethylene glycol-coated (PEGylated) liposomal doxorubicin: rationale for use in solid tumors. Drugs 1997; 54: 15–21

    Article  PubMed  CAS  Google Scholar 

  55. Perret R, Skoulios A. Synthese et caracterisation de copolymeres sequences polyoxyethylene/poly-e-caprolactone. Makromol Chem 1972; 156: 143–56

    Article  CAS  Google Scholar 

  56. Wang S, Qiu B. Polycaprolactone-poly(ethylene glycol) block copolymer: I. Synthesis and degradability in vitro. Polym Adv Technol 1993; 4: 363–6

    Article  Google Scholar 

  57. Younes H, Cohn D. Morphological study of biodegradable PEO/PLA block copolymers. J Biomed Mater Res 1987; 21: 1301–16

    Article  PubMed  CAS  Google Scholar 

  58. Jedlinski Z, Kurcok P, Walach W, et al. Polymerization of lactones, 17a) synthesis of ethylene glycol-L-lactide block copolymers. Makromol Chem 1993; 194: 1681–9

    Article  CAS  Google Scholar 

  59. Liu H, Hu D. Melting behaviour of hydrolyzable poly(oxyethylene)/poly (L-lactide) copolymers. Makromol Chem 1993; 194: 3393–403

    Article  CAS  Google Scholar 

  60. Pitt C, Wang J, Shah S, et al. ESR spectroscopy as a probe of the morphology of hydrogels and polymer-polymer blends. Macromolecules 1993; 26: 2159–64

    Article  CAS  Google Scholar 

  61. Kricheldorf H, Meier HJ. Polylactones, 22a) ABA triblock copolymers of L-lactide and poly(ethylene glycol). Makromol Chem 1993; 194: 715–25

    Article  CAS  Google Scholar 

  62. Cerrai P, Tricoli M. Block copolymers from L-lactide and poly(ethylene glycol) through a non-catalyzed route. Makromol Chem Rapid Commun 1994; 14: 529–38

    Article  Google Scholar 

  63. Zhu K, Xiangzhou L, Shilin Y. Preparation, characterization and properties of polylactide (PLA)-poly(ethylene glycol) (PEG) copolymers: a potential drug carrier. J Appl Polym Sci 1990; 39: 1–9

    Article  CAS  Google Scholar 

  64. Piskin E, Kaitian X, Denkbas EB, et al. Novel PDLLA/PEG copolymer micelles as drug carriers. J Biomater Sci Polym Ed 1995; 7: 359–73

    Article  PubMed  CAS  Google Scholar 

  65. Deng X, Xiong C, Cheng L, et al. Synthesis and characterisation of block copolymers from D, L-lactide and poly(ethylene glycol) with stannous chloride. J Polym Sci: Part C, Polym Lett 1990; 28: 411–6

    Article  CAS  Google Scholar 

  66. Stolnik S, Dunn SE, Garnett MC, et al. Surface modification of poly (lactide-co-glycolide) nanospheres by degradable poly(lactide)-poly(ethylene glycol) co-polymers. Pharm Res 1995; 11: 1800–8

    Article  Google Scholar 

  67. Li Y, Kissel T. Synthesis and characterization of biodegradable ABA triblock copolymers consisting of poly(L-lactic acid) or poly (L-lactic-co-glycolic acid) attached to central poly(oxyethylene) B blocks. J Control Release 1993; 27: 247–57

    Article  CAS  Google Scholar 

  68. Kim TH, Lee H, Park TG. PEGylated recombinant human epidermal growth factor (rhEGF) for sustained release from biodegradable PLGA microspheres. Bio-materials 2002; 23: 2311–7

    CAS  Google Scholar 

  69. Brigger I, Morizet J, Aubert G, et al. Poly(ethylene glycol)-coated hexadecylcyanoacrylate nanospheres display a combined effect for brain tumor targeting. J Pharmacol Exp Ther 2002; 303: 928–36

    Article  PubMed  CAS  Google Scholar 

  70. Calvo P, Gouritin B, Villarroya H, et al. Quantification and localization of PEGylated polycyanoacrylate nanoparticles in brain and spinal cord during experimental allergic encephalomyelitis in the rat. Eur J Neurosci 2002; 15: 1317–26

    Article  PubMed  Google Scholar 

  71. Calvo P, Gouritin B, Chacun H, et al. Long-circulating PEGylated polycyanoacrylate nanoparticles as new drug carrier for brain delivery. Pharm Res 2001; 18: 1157–66

    Article  PubMed  CAS  Google Scholar 

  72. Li YP, Pei YY, Zhou ZH, et al. PEGylated polycyanoacrylate nanoparticles as tumor necrosis factor-alpha carriers. J Control Release 2001; 71: 287–96

    Article  PubMed  Google Scholar 

  73. Morita T, Horikiri Y, Suzuki T, et al. Preparation of gelatin microparticles by co-lyophilization with poly(ethylene glycol): characterization and application to entrapment into biodegradable microspheres. Int J Pharm 2001; 219: 127–37

    Article  PubMed  CAS  Google Scholar 

  74. Caputo A, Betti M, Altavilla G, et al. Micellar-type complexes of tailor-made synthetic block copolymers containing the HIV-1 tat DNA for vaccine application. Vaccine 2002; 20: 2303–17

    Article  PubMed  CAS  Google Scholar 

  75. Faraasen S, Voros J, Csucs G, et al. Ligand-specific targeting of microspheres to phagocytes by surface modification with poly(L-lysine)-grafted poly(ethylene glycol) conjugate. Pharm Res 2003; 20: 237–46

    Article  PubMed  CAS  Google Scholar 

  76. Najafi F, Sarbolouki MN. Biodegradable micelles/polymersomes from fumaric/sebacic acids and poly(ethylene glycol). Biomaterials 2003; 24: 1175–82

    Article  PubMed  CAS  Google Scholar 

  77. Zhang JX, Hansen CB, Allen TM, et al. Lipid-derivatized poly(ethylene glycol) micellar formulations of benzoporphyrin derivatives. J Control Release 2003; 86: 323–38

    Article  PubMed  CAS  Google Scholar 

  78. Artursson P, Brown L, Dix J, et al. Preparation of sterically stabilized nanoparticles by desolvation from graft copolymers. J Polym Sci Part A: Polym Chem 1990; 28: 2651–63

    Article  CAS  Google Scholar 

  79. Gbadamosi JK, Hunter AC, Moghimi SM. PEGylation of microspheres generates a heterogenous population of particles with differential surface characteristics and biological performance. FEBS Lett 2002; 532: 338–44

    Article  PubMed  CAS  Google Scholar 

  80. Sinha VR, Trehan A. Biodegradable microspheres for protein delivery. J Control Release 2003; 90: 261–80

    Article  PubMed  CAS  Google Scholar 

  81. Lee H, Jang IH, Ryu SH, et al. N-terminal site-specific mono-PEGylation of epidermal growth factor. Pharm Res 2003; 20: 818–25

    Article  PubMed  CAS  Google Scholar 

  82. Yamamoto Y, Tsutsumi Y, Yoshioka Y, et al. Site specific PEGylation of a lysine-deficient TNF-alpha with full bioactivity. Nat Biotechnol 2003; 21: 546–52

    Article  PubMed  CAS  Google Scholar 

  83. Manjula BN, Tsai A, Upadhya R, et al. Site-specific PEGylation of hemoglobin at Cys-93(beta): correlation between colligative properties of the PEGylated protein and the length of the conjugated PEG chain. Bioconjug Chem 2003; 14: 464–72

    Article  PubMed  CAS  Google Scholar 

  84. Portales P, Reynes J, Rouzier PR, et al. Perform expression in T cells and virological response to PEG-interferon alpha2b in HIV-1 infection. AIDS 2003; 17: 505–11

    Article  PubMed  CAS  Google Scholar 

  85. Diwan M, Park TG. Stabilization of recombinant interferon-alpha by PEGylation for encapsulation in PLGA microspheres. Int J Pharm 2003; 252: 111–22

    Article  PubMed  CAS  Google Scholar 

  86. Kim JJ, Park K. Glucose-binding property of pegylated concanavalin A. Pharm Res 2001; 18: 794–9

    Article  PubMed  CAS  Google Scholar 

  87. Cantin AM, Woods DE, Cloutier D, et al. Polyethylene glycol conjugation at Cys232 prolongs the half-life of alpha 1 proteinase inhibitor. Am J Respir Cell Mol Biol 2002; 27: 659–65

    PubMed  CAS  Google Scholar 

  88. Zhou S, Liao X, Li X, et al. Poly-D,L-lactide-co-poly(ethylene glycol) microspheres as potential vaccine delivery systems. J Control Release 2003; 86: 195–205

    Article  PubMed  CAS  Google Scholar 

  89. Hawley AE, Illum L, Davis SS. Lymph node localisation of biodegradable nano-spheres surface modified with poloxamer and poloxamine block co-polymers. FEBS Lett 1997; 400: 319–23

    Article  PubMed  CAS  Google Scholar 

  90. Hawley AE, Illum L, Davis SS. Preparation of biodegradable, surface engineered PLGA nanospheres with enhanced lymphatic drainage and lymph node uptake. Pharm Res 1997; 14: 657–61

    Article  PubMed  CAS  Google Scholar 

  91. Gabizon AA. Stealth liposomes and tumor targeting: one step further in the quest for the magic bullet. Clin Cancer Res 2001; 7: 223–5

    PubMed  CAS  Google Scholar 

  92. Cattel L, Ceruti M, Dosio F. From conventional to stealth liposomes: a new frontier in cancer chemotherapy. Tumori 2003; 89: 237–49

    PubMed  CAS  Google Scholar 

  93. Gabizon A, Shmeeda H, Barenholz Y. Pharmacokinetics of pegylated liposomal doxorubicin: review of animal and human studies. Clin Pharmacokinet 2003; 42: 419–36

    Article  PubMed  CAS  Google Scholar 

  94. Harrington KJ, Rowlinson-Busza G, Syrigos KN, et al. The effect of irradiation on the biodistribution of radiolabeled pegylated liposomes. Int J Radiat Oncol Biol Phys 2001; 50: 809–20

    Article  PubMed  CAS  Google Scholar 

  95. Harrington KJ, Mohammadtaghi S, Uster PS, et al. Effective targeting of solid tumors in patients with locally advanced cancers by radiolabeled pegylated liposomes. Clin Cancer Res 2001; 7: 243–54

    PubMed  CAS  Google Scholar 

  96. Harrington KJ, Rowlinson-Busza G, Syrigos KN, et al. Pegylated liposome-encapsulated doxorubicin and cisplatin enhance the effect of radiotherapy in a tumor xenograft model. Clin Cancer Res 2000; 6: 4939–49

    PubMed  CAS  Google Scholar 

  97. Crosasso P, Ceruti M, Brusa P, et al. Preparation, characterization and properties of sterically stabilized paclitaxel-containing liposomes. J Control Release 2000; 63: 19–30

    Article  PubMed  CAS  Google Scholar 

  98. Torchilin VP, Levchenko TS. TAT-liposomes: a novel intracellular drug carrier. Curr Protein Pept Sci 2003; 4: 133–40

    Article  PubMed  CAS  Google Scholar 

  99. de Melo AL, Silva-Barcellos NM, Demicheli C, et al. Enhanced schistosomicidal efficacy of tartar emetic encapsulated in pegylated liposomes. Int J Pharm 2003; 255: 227–30

    Article  PubMed  CAS  Google Scholar 

  100. Ishida T, Maeda R, Ichihara M, et al. Accelerated clearance of PEGylated liposomes in rats after repeated injections. J Control Release 2003; 88: 35–42

    Article  PubMed  CAS  Google Scholar 

  101. Pratt L, Chu C. Hydrolytic degradation of a-substituted polyglycolic acids: a semiempirical computational study. J Comput Chem 1993; 14: 809–17

    Article  CAS  Google Scholar 

  102. Younes H, Nataf P, Cohn D, et al. Biodegradable PELA copolymers: in vitro degradation and tissue reaction. Biomater Artif Cells Artif Organs 1988; 16: 705–19

    PubMed  CAS  Google Scholar 

  103. Fresta M, Fontana G, Bucolo C, et al. Ocular tolerability and in vivo bioavailability of poly(ethylene glycol) (PEG)-coated polyethyl-2-cyanoacrylate nanosphere-encapsulated acyclovir. J Pharm Sci 2001; 90: 288–97

    Article  PubMed  CAS  Google Scholar 

  104. Allemann E, Brasseur N, Benrezzak O, et al. PEG-coated poly(lactic acid) nanoparticles for the delivery of hexadecafluoro zinc phthalocyanine to EMT-6 mouse mammary tumours. J Pharm Pharmacol 1995; 47: 382–7

    Article  PubMed  CAS  Google Scholar 

  105. Bazile D, Verecchia T, Bassoulet M, et al. Ultradispersed polymer systems with rate and time control. Yanuzaigaku 1993; 53: 10

    CAS  Google Scholar 

  106. Brigger I, Chaminade P, Marsaud V, et al. Tamoxifen encapsulation within polyethylene glycol-coated nanospheres: a new antiestrogen formulation. Int J Pharm 2001; 214: 37–42

    Article  PubMed  CAS  Google Scholar 

  107. Gupta P, Hung C. Targeted delivery of low dose doxorubicin hydrochloride administered via magnetic albumin microspheres in rats. J Microencapsul 1990; 7: 85–94

    Article  PubMed  CAS  Google Scholar 

  108. Lalla J, Ahuja P. Drug targeting using non-magnetic and magnetic albumin globulin mix microspheres of melefamic acid. J Microencapsul 1991; 8: 37–52

    Article  PubMed  CAS  Google Scholar 

  109. Hassan E, Gallo J. Targeting of anticancer drugs to the brain: I. Enhanced brain delivery of oxantrazole following administration in magnetic cationic microspheres. J Drug Target 1993; 1: 7–14

    Article  PubMed  CAS  Google Scholar 

  110. Wagner E, Zenke M, Cotten M, et al. Transferrin-polycation conjugates as carriers for DNA uptake into cells. Proc Natl Acad Sci U S A 1990; 87: 3410–4

    Article  PubMed  CAS  Google Scholar 

  111. Kreuter J. Nanoparticles. In: Kreuter J, editor. Colloidal drug delivery systems. New York: Marcel Dekker, 1994: 315

    Google Scholar 

  112. Gref R, Luck M, Quellec P, et al. Stealth corona-core nanoparticles surface modified by polyethylene glycol (PEG): influences of the corona (PEG chain length and surface density) and of the core composition on phagocytic uptake and plasma protein adsorption. Colloids Surf B Biointerfaces 2000; 18: 301–13

    Article  PubMed  CAS  Google Scholar 

  113. Jagur GJ. Biomedical application of functional polymers. React Funct Polym 1999; 39: 99–138

    Article  Google Scholar 

  114. Hrkach JS, Peracchia MT, Domb A, et al. Nanotechnology for biomaterials engineering: structural characterization of amphiphilic polymeric nanoparticles by 1H NMR spectroscopy. Biomaterials 1997; 18: 27–30

    Article  PubMed  CAS  Google Scholar 

  115. Moghimi SM. Chemical camouflage of nanospheres with a poorly reactive surface: towards development of stealth and target specific nanocarriers. Biochim Biophys Acta 2002; 1590: 131–9

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

We are thankful to the University Grants Commission for providing us financial assistance. The authors have no conflicts of interest that are directly relevant to the content of this review.

Author information

Authors and Affiliations

  1. Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160014, India

    Vivek Ranjan Sinha, Ashu Aggarwal & Aman Trehan

Authors
  1. Vivek Ranjan Sinha
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ashu Aggarwal
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Aman Trehan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vivek Ranjan Sinha.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sinha, V.R., Aggarwal, A. & Trehan, A. Biodegradable PEGylated microspheres and nanospheres. Am J Drug Deliv 2, 157–171 (2004). https://doi.org/10.2165/00137696-200402030-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00137696-200402030-00002

Keywords

Search

Navigation